Herbal medicines or herbal drugs are of ancient origin and their use is known in cultures throughout the world. In India science of herbal medicine known as “ayurveda” medicine, which gives us the modern term “ayurvedic,” derived from “ayur,” meaning life and “veda” meaning knowledge. A movement to identify individual active ingredients in beneficial herbs developed in the 18th century, leading into a transitional period from the use of natural herbs to the use of pharmaceutical drugs such as extracts and purified chemicals, sometimes referred to as allopathic drugs. With advances in chemistry, some of the active ingredients were chemically synthesized and given to patients in the form of pills. However, during this time of transition, the synthesized, purified or extracted active ingredients of pharmaceutical drugs were observed to exhibit significant adverse side effects.
Generally, herbal medicines do not produce significant side effects, perhaps because the active ingredients are combined with other compounds in the herb and administered in different dosages. In addition, herbs often are administered in combinations, which may nullify the side effect of any one herb. However, purified pharmaceutical drugs seldom are administered in combinations to offset each other's side effects, perhaps because even the offsetting drug is likely to produce its own side effects. It appears that modern medical practice accepts the presence of side effects as an adjunct to the improved purity and efficacy of pharmaceutical drugs. Modern drug synthesis has the advantages of providing pure and potent drugs in large quantities and with considerable speed for wide availability. However, the accompanying problem of side effects is gaining increased notice as the public justly criticizes that such pure and potent drugs can cure one ailment while causing another.
Several plants species are known to have helped in cure, treatment of periodontal diseases, particularly in alleviation of tooth aches. In the literature, several plants have been referred to as commonly used plants for dental care. In recent years, on account of adverse effects of synthetic drugs, attempts have been made upon the potential of phytochemicals for the prevention and treatment of periodontal diseases. Various plant preparations like Azadirachta indica (1), Acacia (2), Oolong tea (3), Juglans regia (4, 5), Zanthoxylum alantum (5), Mimusops elengi (5) and Hibiscus abelmoschus (5) etc. have been used for the prevention of periodontal diseases.
There have been several reviews on neem, however most of these relate to its pesticidal properties (6–8). Almost every part of the tree has long been used in traditional folklore medicines for the treatments of a variety of human ailments, particularly against diseases of bacterial and fungal origin. Antibacterial and antifungal (9) anti-malarial (10, 11), antipyretic and anti-inflammatory (12) are the most frequently cited uses of neem.
Andrew et al. (13) reported that neem is a part of Ayurvedic and folk medicine in India and has a potential for several remedies. Gahukar (14) reported use of neem twigs for pyorrhoea infection. Wolinsky et al (15) investigated bactericidal properties of neem extract.
Their studies with aqueous extracts revealed that bacterial properties are altered and ability of Streptococci to colonize tooth surface are inhibited. Farooqi et al. (16) reported that Azadirachta indica stem are used as chewing sticks. Guhabakshi et al. (17) reported that different parts of neem (Azadirachta indica) such as young branches are used as tooth brushes, particularly in pyorrhoea; and decoction of leaves for washing septic wounds, etc. African members of the Meliaceae such as the Crabwood or Monkey Cola Tree (Carapa procera) and Dry Zone Mahogany (Khaya senegalensis) are also used as chewing-sticks, and like neem are used to heal (particularly skin and oral infections) and treat malaria (18, 19).
Effect of chewing sticks of neem on dental health has been attributed to presence of fluorides in plants parts. Chawala (20) reported that 20% w/v aqueous extracts of a neem chewing-stick (presence of bark unknown) yielded 2.8 ppm fluoride. Presence of fluoride has been reported to prevent accumulation of bacteria on teeth.
Chewing sticks of Azadirachta indica and Salvadora persica (“Miswak”) were tested for their antimicrobial activity using various concentrations. Both the chewing sticks were effective against Streptococcus mutans, and S. faecalis (21) Arak extract was more effective at lower concentrations against S. faecalis. This difference was attributed to the difference in their pH values.
Neem bark contains tannins and 8 to 11 percent of anti-inflammatory polysaccharides (Terumo Corporation, U.S. Pat. No. 4,515,785). These polysaccharides contain glucose, arabinose and fructose in an approximate ratio of 1:1:1. Apart from these several diterpenoids (Nimbosodione; Nimbisonol; Demethyl Nimbiolon; Margosone; Margosolone; Nimbonone; Nimbonolone; Nimbionone; Nimbionol; Nimbione; Nimbinone and C-seco tetranortriterpenoids iso-nimbionlide) have also been reported.
Masaki Shimizu et al. (22) patented a process to extract neem bark using solvents like benzene and toluene, etc. The extract was found to retard growth of sarcoma tumours in mice. However, later they extended the patent by reporting extraction in alcohol after treating bark with water at 0° to 40° C.
In 1966 there were only three known triterpenoids from neem. Studies of Jarvis and Morgan (23) on the antifeedant properties in neem seeds led to azadirachtin stimulated research, so that many other compounds were isolated in the 1970's and 1980's from neem (24). Today there are more than 145 known neem triterpenoids, and there must be others yet to be discovered. Little more than one third of these have been tested for biological properties. Many of these triterpenoids (25, 26) have been isolated from neem oil.
Four neem limonoids: gedunin, dihydrogedunin nimbinin, and nimbolide reportedly possess LC50 values of 0.72 to 1.74 μg/ml against P. falciparum in vitro (27). Some rural communities in Kenya are already using neem for alternate preventive and curative treatment against malaria. A survey of communities in Western Kenya, bordering Lake Victoria, revealed that 98% members of the communities knew about neem; 36% had actually used neem for malaria prevention and treatment (28). They got relief by using bark or leaves boiled in water; some used seed powder dissolved in warm water, or a mixture of neem leaves, bark, and roots boiled in water. These preparations were administered at 1 to 2 glasses twice or thrice a day until recovery as few chewed neem leaves several times a day; other inhaled neem leaf smoke thrice a day.
Use of neem oil is becoming popular for treating ringworm (Tinea species) among children in rural Kenya (29). Application of a paste made from neem leaves and turmeric in 4:1 proportion to the skin reportedly cured 97% of the patients suffering from scabies caused by the itch mite, Sarcoptes scabei in 3–15 d (30). In Kenya, severe cases of scabies in children are getting cured by bathing with water from boiled leaves and then applying neem oil on affected body parts (29).
Voorhees J. & Nachman L. used 5 to 10% neem leaf powder along with 80 to 88% olive leaf extract and homeopathic blend for preparing a composition for treating symptoms of influenza (U.S. Pat. No. 6,455,070 (Publication No. 2002/0110600).
Wolf et al. (U.S. Pat. No. 6,228,402) have reported a Xylitol containing non-human food stuff for a treatment for reducing the incidence of dental carries in animals (31). They have (not as a claim) but as a suggestion reported that other ingredients including neem oil can be used.
U.S. patent application Ser. No. 07/456,762 and U.S. Pat. No. 5,298,251 (Locke et al.) teach that non-polar hydrophobic solvent extracts of ground neem seed yield a neem oil product that can have combined insecticidal and fungicidal activities. They reported that clarified neem oil demonstrates increased insect repellence, decreased phyto-toxicity, decreased skin irritability, increased fungicidal activity and increased wetting ability. The neem wax demonstrates increased insect repellence, increased fungicidal activity and increased wetting ability (32).
There have been several other patents on neem but these are primarily on use of neem as pesticide or neem based pesticidal stable formulations such as U.S. Pat. No. 4,556,562 (Stable anti-pest neem seed extract); U.S. Pat. No. 4,902,713 (azadirachtin like compound and insect destroyed agents); U.S. Pat. No. 4,943,434 (insecticidal hydrogenated neem extract); U.S. Pat. No. 4,946,681 (method to prepare in improved storage stable neem seed extract); U.S. Pat. No. 4,960,791 (salanin derivation insect control agents); U.S. Pat. No. 5,001,146 (storage stable azadirachtin formulation); U.S. Pat. No. 5,001,149 (azadirachtin derivative insecticides); U.S. Pat. No. 5,047,242 (azadirachtin derivative insecticides); U.S. Pat. No. 5,110,591 (neem oil emulsifier); U.S. Pat. No. 5,124,49 (storage stable azadirachtin formulations); and U.S. Pat. No. 0,436,257 (method of controlling fungi on plants by the aid of hydrophobic extracted neem oil).
Citrullus colocynthis Schrad, a member of family Cucurbitaceae, commonly known as “indrayan”, “tumba”, “Ghorumba”, “kaur-tumba”, “tumba”, “tumbi” or bitter apple is a wild plant. It has also been referred by its earlier name Citrullus vulgaris. Colocynth is most abundant in north-western plains of India, especially in the Barmer, Bikaner, Jaisalmer and Jodhpur districts of Rajasthan, and in Gujarat where it forms large patches on sand dunes, sandy undulating plains and inter-dunal areas; occurs wild throughout India particularly in the Northwest, Central and South India and on the sea shores of the Coromandal coast, Gujarat, and other parts of Western India. In recent years colocynth has found a place in the oil industry of western Rajasthan. Thus, its cultivation in Rajasthan serves three purposes, viz. continuous supply of seed (as cash crop) to oil industry for soap-making; stabilization of shifting sand, and checking the danger of its becoming extinct due to over exploitation.
The fruits and seeds are occasionally used as food in parts of Africa. The gourds are eaten after pickling which makes them safe for eating. They are made into preserves after boiling thoroughly in water to remove their bitterness. They are also used as vegetable after removing their rind. The stem and leaves are eaten by goats and wild game (33–36). Its fruits and seeds have purgative properties, while roots are used as purgatives, used in ascites, jaundice, urinary diseases and rheumatism. These are also used against snake poison. The bitter substance has been reported to be colocynthin and colocynthetin (Amer. J. Pharm., 1893, 179; Pharm. J., 1907, 117; Arch. Harm., Berl., 1883, 201; J. Chem. Soc., 1910, 99; Indian J. med. Res., 1929, 770); roots contain alpha-elaterin, hentria-contane, and saponins (Curr. Sci., 1934, 350); and seeds contain fixed oil, a phytosterolin, phytosterols, hydroxyl carbons, saponins, glycosides and tannin (J. Indian chem. Soc., 1949, 515, 519); pulp contains alpha-elaterin, hentriacontane, a phytosterol and a mixture of fatty acids (B.P.C. 1934, 348) (37–41).
Okieimen et al. (42) reported removal of heavy ions from aqueous solution with melon (Citrullus vulgaris) seed husks (Biological Wastes: 0269, 7483, 1989). Citrullus vulgaris Schrad has been proposed as an effective feeding stimulant (U.S. Pat. No. 5,968,541). Citrullus colocynthis has been used, as a powder, to impart bitter flavour to the composition for topical animal medication such as to prevent common house pets such as dogs and cats from licking their wounds. The claim made in the patent is for use only as a bittering agent (U.S. Pat. No. 6,274,555).
Citrullus colocynthis contains several bitter principals; cucurbitacin is one of the major ones present in several genera of the family Cucurbitaceae. The cucurbitacin are a group of bitter-tasting, highly oxygenated, mainly tetra cyclic, triterpenic plant substances derived from the cucurbitane skeleton (43). These compounds are present in many plants and function as an allomone to protect the plants from herbivores (44). In addition, the cucurbitacins are known to have purgative, anti-inflammatory, anti-fungal, and anti-cancer properties (45); and anticancer agents based on natural product models (46).
Commercialization of cucurbitacin-based products has been very limited because (a) the triterpenes are secreted in very small quantities in cucurbitaceous plants, and (b) the existing procedures involved in obtaining pure cucurbitacin is lengthy and burdensome (47). The difficulties involved in obtaining large quantities of cucurbitacins in the past have discouraged serious pursuit of most potential uses of this triterpenes. McMahon et al. (48) taught controlled-release microcapsules that contain insecticides and other compounds useful in crop management. In one embodiment of the invention, the capsule wall contains an anti-feedant compound comprising cucurbitacin-containing solid particles, powder or dust (48). The preferred cucurbitacin-containing solids used are in the form of dried, ground, gourd roots as described in U.S. Pat. No. 4,880,624.
Branly et al. (49) describes baits for diabroticite beetles containing a feeding stimulant and an insecticide. The feeding stimulant comprises plant tissue containing cucurbitacin, and more specifically comprises dried buffalo gourd root in an amount of 10–100 lb. of ground root per acre. Based on this technology, a cucurbitacin-dependent control method for adult cucumber beetles has reportedly been developed. By lacing cucurbitacin-containing plant tissue with insecticide, the beetles are “tricked” by the feeding-stimulant cucurbitacin into eating the toxins.
Ground root tissue containing cucurbitacin has been used as broadcasted bait capable of killing 99% of the diabroticite beetles consuming it (47, 50). However, it is reported that this form of cucurbitacin is effective in the control of adult beetles only, while much of the damage caused by the diabroticite beetles is caused by the larval form (51). The use of purified cucurbitacins in place of plant tissue is one possible solution to this problem, as purified cucurbitacin has been shown to be an effective feeding stimulant for diabroticite beetles in both adult and larval forms. Unfortunately, there are no products marketed today that utilize purified cucurbitacin.
Berdami; L. A. (52) developed a composition and method for topical animal medication consisting of bacitracin zinc, neomycin, polymycin-B sulfate, and pramoxine hydrochiomide. They used Citrullus colocynthis as a bittering agent to impart a bitter flavor to the composition such as to prevent common house pets, such as dogs or cats, from licking their wounds.
Subbiah, V. (53) describes a method of isolating and purifying cucurbitacins from Cucurbita species (not Citrullus colocynthis). Most of the earlier studies on application of cucurbitacin are from Cucurbita speciea and not Citrullus colocynthis. However, Hatam et el (54) have isolated cucurbitacin glycosides from Citrullus colocynthis. 
Main diseases of the teeth include plaque, carries and pyorrhoea. Dental plaque is the main cause of most of the periodontal diseases (55, 56). Plaque control is the only effective method of controlling chronic periodontal diseases. People use mechanical devices to control plaque. These are tooth brush used with tooth paste, abrasive powders, inter-dental cleaning aids, oral irrigation devices etc. However, these practices have several limitations and the entire tooth surface cannot be cleaned. Moreover, once plaque is deposited in substantial quantities, it is difficult to remove with common mechanical methods. Once plaque is deposited, this leads to other diseases. These mechanical aids are not therapeutic in activity; hence chemotherapeutic agents remain in demand for periodontal diseases.
Prominent among the chemicals used are antibiotics (57), enzymes (58), dextrose (59), chlorhexidine (60), urea peroxide (61), organic and inorganic fluorides (62) and ammonium compounds (63) etc. Many of these products are effective to some extent but either are limited in their use or have side effects. Earlier several plant species have been used for dental care.
Some of plants used as dental care are:
TABLE 1#NameActivity1Acacia catechuPaste used for Bleedinggums and toothhypersensitivity2Acacia niloticaTwigs as tooth brush3Achyrathes asperaTwigs as tooth brush4Azadirachta indicaTwigs as tooth brush5Aristolochia bracteolataRoot juice applied at thesite of pain6Carapa proceraTwigs as tooth brush; oralinfections7Cinnamomum camphoraPaste applied or tendertwigs chewed8Cinnamomum verumPowdered stem bark isapplied to teeth in thetreatment of caries andpyorrhea9Curcuma longaPowder of rhizome is usedin tooth powder for curingpyorrhea10Eucalyptus globulusLeaf oil used to preventtooth decay and relief ofpain11Ficus bengalensisAerial root is used as toothbrush and the latex isapplied in toothache12Juglans regiaStem bark used in toothpowders for healthy teeth13Hibiscus abelmoschusAs paste or powder14Khaya senegalensisTwigs as tooth brush; oralinfections15Madhuca longifoliaStem bark used in toothpowders for gum pain andtoothaches.16Mimusops elengiStem bark used in toothpowders for gum pain andtoothaches.17Myristica fragransFruit paste is applied onteeth to cure dental cariesand pyorrhea18Ocimum sanctumLeaves paste used for toothhypersensitivity19Oolonga teaAs tea or mouth wash20Piper betelLeaves paste used for toothhypersensitivity21Piper longumFruit powder used againstdental carries.22Piper nigrumFine powder of seeds isapplied for tooth ache andpyorrhea and bleedinggums.23Potentilla fulgensRoot powder is applied ingingivitis24Punica granatumStem bark or fruit rind isused in tooth powders.25Salvadora persicaTwigs as tooth brush; rootsagainst dental carries.26Syzygium aromaticumClove oil is applied fortoothache, dental caries andpyorrhea27Spilanthes calvaFlowers chewed intoothache.28Zanthoxylum armatumTwigs as tooth brush; fruitsapplied to teeth intoothache.
These plants have been reported as effective anti-plaque inhibitors without any side effects. Some of the herbal extracts especially neem in “in vitro” studies have also shown inhibition of Staphylococcus aureus, Streptococcus pyogens and anaerobes. These “in vitro” studies support the anti plaque potentiality of neem.
Neem has been used as a component of toothpastes, mouthwashes, food compositions gingivitis, for reducing caries and treatment of inflammation of the mouth, as a natural flavoring agent in oral compositions used for treating plaque and gingivitis (64–66).
It has also been used as a component of chewing gum containing a teeth whitening agent (67).
Ahmad, et al. (68) used micro-sized particles or microfibers of branches or roots of plants named by them as Azadirachta or Salvadora persica, and commonly known in different parts of the world as the peelu, miswaak, neem or siwak tree. They used these particles in place of commonly used mineral abrasives.
Scheller (69) in his patent (U.S. Pat. No. 4,223,003) used neem oil as one of the optional components of their paste and powder dentifrices.
Miller S. E. and Simone A. J. reported formulation of chewing sticks made from natural fibbers. They suggested use of neem oil but no claim to its properties was made. Also no description of extraction of oil or plant parts used was given (70).
Nabi et al (71) reported a formulation comprising thymol and eugenol, and optionally a sesquiterpene alcohol. They claimed the formulation to have plaque and gingivitis effects. They suggested use of neem oil to provide an organoleptically acceptable oral product.
Seabrook, Jr. et al. suggested use of neem seed, leaf, bark extracts and oil in their formulations of polymers containing antimicrobial agents. They suggested that the antimicrobial agents include phytochemicals and phyto-nutrients such as naturally occurring extracts from plants and herbs and other chemical disinfectants (72).
At present, a number of tooth powders which contain cheap pulverized items that are not very effective as well as harmful for gums and teeth and have toxic effects are available in India. Compositions of some of the herbal tooth powders as available in market are given below:
Product nameManufacturerIngredientsRed Tooth PowderDabur India Ltd., 22,Pudina sativa (Mentha sp.), avang kaSite IV Sahibabad,tail, Tomer beej (ZanthoxylumGhaziabad, Indiaacanthopodium), Kapoor, Kalimarich(Piper nigrum), Pippali (Piper longum),Sunthi (Zingiber officinale), Tambaku(Nicotiana tabacum)Vicco VajradantiVicco Laboratories, 25,Babbul (Acacia nilotica), Janibhul,Jerbi Wadia Road,Lavang (Syzygium aromaticum),Parel, Bombay-400012,Manjishtha (Rubia cordifolia), Dalchini,India(Cinnamomum zeylanicum), Vajradanti(Potentilla fulgens), Acrod, Khairpatang, Akkal Kadha, Babul,Jeshthamadh, Kabachini (Pipercubaba), Anant root, (Hemidesmusindicus), Ajwain, (Trachyspernumammi), Jaifal, (Myristica fragrans),Trifala (Emblica officinal is, Terminaliachabula, Terminalia belerica), ricehusk, sugar, alum, salt.Lordent ToothpowderLord's CosmeticsExtract of Plantago, Calendula andInternational A-21/27,creosoteNaraina Industrial Area,Phase-II, New Delhi-110028, IndiaMeghdoot dantushaMeghdoot Gramodhyog,Sonth (Zingiber officinale), SevaSeva Sansthan,Sansthan, Pipal (Ficus religiosa),Meghdoot Building,Kalimirch (Piper nigrum, Tomar beejChandganj Garden,(Zanthoxylum acanthopodium),Lucknow, IndiaSamundar Jhag, Akarkara (Anacycluspyrethrum) Manjuphal, Maulshri(Mimosops elengi), Sengdha salt.PayorinDawakhana Tibbiya,Amla (Emblica officinalis), Sokhta, GileCollege, AMU, Aligarhgaimuliya, Taj galmi, Kafoor khlis,HamizeHamdard ManjanHamdard (Wakf)Ilaichi (Electtaria cardamomum) kalan,Laboratories, HamdardAmla (Emblica officinalis), halaila zardMarg, Delhi, India(Terminalia chebula), Banslochan,Bambusa bambos), Zanjbeel, Zingiberofficinale), Sangjarahat, Filfil siyah(Piper nigrum), Kabab khandan,Khoolanjan (Alpinia galanga), NamakSambhar, Mileh firangi, Sat paudina(Mentha spp)MDH DantSuper Delicocies Pvt.Acacia nilotica, Embelia tsjenam-powderLtd.cottam, Areca catechu, Juglansregia, Curcuma amada, Syzygiumaromaticum, Alpinia galangal, Ficuselastica, Piper nigrum, Menthol,Eucalyptus oil.PayakilGurukul Pharmacy,Acacia nilotica, Juglans regia,Haridwar, IndiaCamphora officinatum, Azadirachtaindica, Arcila vitrolutcum, ZanthoxylumarmatumCritical Review of Earlier Patents/Prior Art    Data related to clinic value of neem used as chewing sticks are rare and only in generic forms.    Formulations are crudely prepared as aqueous solutions, chewing sticks, or leaf and bark extracts.    Claims are made of effect of azadirachtin (from neem) in formulations; azadirachtins have been reported to have insect antifeedant and repellent properties and there are no claims for dental protection.    Some of the commercial dental care formulations suffer from a number of disadvantages. Some stain teeth and gums. Most of these products lack standardization.    No prior art of use of Citrullus colocynthis for dental cure, alone or in combination of Azadirachta indica     Majority of patents and formulations (quoted in the text) are on pesticidal activities for filed crop of neem.    Berdami, L. A. (U.S. Pat. No. 6,274,555) used Citrullus colocynthis as a bittering agent in their composition for topical animal medication. They used a few grains of Citrullus colocynthis as a bittering agent to impart a bitter flavor to the composition such as to prevent common house pets, such as dogs or cats, from licking their wounds. No claim with respect to cure for plaque or gingivitis was made. Moreover they did not use roots of Citrullus colocynthis.     Cucurbitacins from Citrullus like plants has been used as in U.S. Pat. No. 5,466,460 as an antifeedant compound in the walls of capsules containing targeted insecticide. The use thus is only as an antifeedant.    Locke et al. (U.S. Pat. No. 5,298,251 and U.S. patent application Ser. No. 07/456,762) reported a fungicidal composition derived from neem oil and neem wax fractions. However they did not use neem leaves and bark and no claim to therapeutical use against dental plaque or gingivitis was made.    Seabrook, Jr. et al. (U.S. Pat. No. 5,906,825) suggested use of neem seed, leaf, bark extracts and oil in their formulations of polymers containing antimicrobial agents. They claimed their use as antimicrobial agents, however, neem was suggested as one of several agents; moreover this was only a suggestion and not a component of the claims of the patent. They also did not describe the extraction procedure and no claim or mention of anti-plaque or anti-gingivitis was made.    U.S. Pat. Nos. 4,515,785 and 4,537,774 by Masaki Shimizu et al. (20) where they reported a procedure to extract neem bark using solvents like benzene and toluene, etc. (the extract was found to retard growth of sarcoma tumours in mice) and later extended the same by reporting extraction in alcohol after treating bark with water at 0° to 40° C. for higher purity does not incorporate cold extraction; or any combination with leaves or any other plant. They have also no claim on dental formulations. Their claim is on anti-tumour properties on sarcoma tumours in mice.    U.S. Pat. No. 6,264,926 by Farooqi et al. (16) reported a synergistic composition comprising the pastes or powders of Zanthoxylum armatum, Zingiber officinale, Sandalwood, Roasted alum, Common salt, Spilanthes calva, Pistacia sp., Quercus infectoria, Usnea longisima in the proportion of 20–25%, 25–30%, 8.25–8.5%, 8–9%, 15–16%, 2–2.5%, 2–2.5%, 8–8.5%, and 1–4% respectively. They did not use either Azadirachta indica or Citrullus colocynthis in their formulation.    Howard H. S. has used (42×) neem oil in chewing gum containing a teeth whitening agent. The neem oil as described in their patent has been taken from neem seeds (not from leaves and bark). Moreover the oil has been extracted using hexane from neem seeds and not leaves and bark. Also they have made no claims to its therapeutical use. Others such as Lewis W. H. (63); Maurice M. I. (64) and U.S. Pat. Nos. 5,371,254; 5,472,684 and HI 541 have reported its utility for gum diseases yet no details of the proportions to be used, methods of extraction and any synergistic effects with other plants have been detailed.    Ahmad et al. (1991) in U.S. Pat. No. 5,009,886 on Dentifrice used micro-sized particles or microfibers of Azadirachta indica or Salvadora. It is not clear if they are botanically correct in naming the plants since they have named neem, peelu, miswaak or siwak as synonyms. In the detailed description they have mentioned only pilu which is botanically Salvadora persica. Moreover they have used wood for preparing abrasive in their dentifrice.    Schellerin's patent on paste and powder dentifrices (U.S. Pat. No. 4,223,003) used neem oil as one of the optional components, however no claim has been made on the benefit they derived by using neem oil. Moreover they have used neem oil apparently derived from neem seeds and not leaves and bark.    Nabi et al. in U.S. Pat. No. 4,223,003 reported a formulation comprising thymol and eugenol, and optionally a sesquiterpene alcohol. They claimed the formulation to have plaque and gingivitis effects. They used neem oil as a flavouring agent, however it was only one the agents selected from the group consisting of Tulsi oil, Neem oil, Eichinacea tincture, rosemary extracts, golden seed extracts, passion flower extract, turmeric extracts, betel nut extracts, sunphenon tea extracts, and dandelion root extracts. Neem oil was used only as a flavouring agent. No details of preparation of neem oil have been given; apparently, it was oil extracted from seeds and not leaves and bark.    Wolf et al. (U.S. Pat. Nos. 5,989,604 and 6,159,508) suggested use of neem oil in their xylitol based formulation for dogs (non-human animals) for reducing the incidence of dental carries. The invention is based on Xylitol, however as a suggestion they have listed several plants such as gum arabic, beef broth, chicken broth or distilled water, lecithin, Coenzyme Q10, folic acid, aloe vera, comfrey, rosemary, goldenseal, horsetail, arnica, calendula, barley grass, chamomile, bloodroot, siwak-miswak, pullulan, horse chestnut, neem, peelu, propolis, green tea, myrrh, birch bark, white oak bark, tea tree oil, grape seed extract, wheat germ, bromelain, papain and quercetincan be added to promote health of hard and soft dental tissue. There was no claim of the inventors as to use of neem as a cure or protection against dental plaque or gingivitis. This was only suggested as one of the several options to promote health of tissue when added to Xylitol. No method of extraction or details of the plant parts used has been given.    Wolf et al. (U.S. Pat. No. 6,228,402) have reported a xylitol containing non-human food stuff for a treatment for reducing the incidence of dental carries in animals. They have as a suggestion added that other ingredients such as XXX can be added to promote health of hard and soft dental tissue. There was no claim of the inventors as to use of neem as a cure or protection against dental plaque or gingivitis. This was only suggested as one of the several options to promote health of tissue.